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Abstract:

Spectroscopic filter arrays and methods for making spectroscopic filter
arrays are provided. The arrays are formed using a dispersion of filter
particles having selected moieties attached to the surface of the
particles and a microarray having complementary moieties formed in an
array on a substrate, such that each filter particle is attached to a
selected region of the microarray. The moiety on the substrate may be RNA
or DNA or other molecule. The substrate may be a surface of a
photodetector array, a transparent plate that may be placed in
registration with the photodetector or a stamp used to transfer the
filter array to a photodetector array.

Claims:

1. An imaging system for electromagnetic radiation, comprising: a
photodetector array; a microarray on a substrate having a plurality of
addressable regions, each addressable region having a layer comprising a
first moiety attached to the substrate; and a plurality of filter
particles, each filter particle having a second moiety attached thereto,
the second moiety being complementary to the first moiety on a selected
addressable region of the microarray.

2. The imaging system of claim 1 wherein the substrate is a surface of
the photodetector array.

3. The imaging system of claim 1 wherein the substrate is a plate
transparent to the region of the electromagnetic spectrum being detected
and the microarray is in registration with the photodetector array.

4. The imaging system of claim 1 wherein the substrate is a stamp that is
used to transfer the plurality of filter particles to the photodetector
array.

5. The imaging system of claim 1 wherein the first moiety is DNA or RNA
and the second moiety is capable of hybridizing with the first moiety.

6. The imaging system of claim 1 further comprising one or more layers of
filter particles.

7. The imaging system of claim 1 wherein the filter particles are
core-dyed microspheres.

8. The imaging system of claim 1 wherein the filter particles are
microparticle- or nanoparticle-impregnated microspheres.

9. The imaging system of claim 1 wherein the filter particles are
microparticles or nanoparticles.

10. The imaging system of claim 1 wherein the filter particles comprise a
pigment or a phosphor for upconverting infrared electromagnetic
radiation.

11. The imaging system of claim 1 wherein the filter particles comprise a
molecular structure that can be vibrationally excited with different
wavelengths of infrared radiation.

12. The imaging system of claim 1 further comprising a linking layer
between the filter particles and the photodetector array.

13. The imaging system of claim 1 further comprising an intermediate
layer between the substrate and the microarray.

14. The imaging system of claim 1 further comprising an outermost layer
having an index of refraction selected to decrease scattering of
electromagnetic radiation in the system.

15. The imaging system of claim 1 wherein the microarray is in a
2.times.2 pixel pattern.

16. The imaging system of claim 1 wherein the microarray is in an
N×N pixel pattern, where N is greater than 2.

17. The imaging system of claim 1 wherein at least a portion of the
microarray is in an N×M pixel pattern, where M is not equal to N.

18. The imaging system of claim 1 wherein at least a portion of the
microarray is in a pixel pattern that is not rectangular.

19. A method for making an imaging system for electromagnetic radiation,
comprising: (a) providing a photodetector array having addressable
regions and a surface; (b) attaching selected biomolecules to selected
addressable regions of the surface; (c) providing first filter particles
having attached thereto complementary biomolecules selected to bind with
the biomolecules in selected addressable regions of the array; (d)
exposing a dispersion of the filter particles to the array to form a
first layer of first filter particles; and (e) removing excess dispersion
from the photodetector array.

20. The method of claim 19 further comprising applying an index-matching
layer after step (e).

21. The method of claim 19 further comprising providing second filter
particles having attached thereto second complementary biomolecules
selected to bind with the biomolecules of the first layer of filter
particles and repeating steps (d) and (e) to form a second layer of
filter particles.

22. A method for making an imaging system for electromagnetic radiation,
comprising: (a) providing a photodetector array having addressable
regions and a surface; (b) providing a transparent plate having a
surface; (c) attaching selected biomolecules to selected addressable
regions of the surface of the transparent plate to form a microarray; (d)
providing first filter particles having attached thereto complementary
biomolecules selected to bind with the biomolecules in the microarray;
(e) exposing a dispersion of the first filter particles to the microarray
to form a first layer of filter particles; (f) removing excess dispersion
from the plate; and (g) placing the transparent plate having the
microarray over the photodetector array such that the microarray is in
registration with selected addressable detectors of the photodetector
array.

23. The method of claim 22 further comprising applying an index-matching
layer after step (f).

24. The method of claim 22 further comprising providing second filter
particles having attached thereto second complementary biomolecules
selected to bind with the biomolecules of the first layer of filter
particles and repeating steps (e) and (f) to form a second layer of
filter particles.

25. A method for making an imaging system for electromagnetic radiation,
comprising: (a) providing a photodetector array having addressable sensor
elements; (b) providing a transfer stamp having a surface; (c) attaching
selected biomolecules to selected regions of the surface of the stamp to
form a microarray; (d) providing filter particles having attached thereto
complementary biomolecules selected to bind with the biomolecules in the
microarray; (e) exposing a dispersion of the filter particles to the
microarray to form a first layer of filter particles; (f) removing excess
dispersion from the stamp; and (g) applying the stamp to the
photodetector array in registration with selected addressable sensor
elements.

26. The method of claim 25 further comprising removing the stamp from the
photodetector array and leaving the filter particles on the
photodetector.

27. The method of claim 25 wherein the photodetector array further
comprises a linking layer

28. The method of claim 25 further comprising applying an index-matching
layer.

29. The method of claim 25 further comprising providing second filter
particles having attached thereto second complementary biomolecules
selected to bind with the biomolecules of the first layer of filter
particles and repeating steps (e), (f) and (g) to form a second layer of
filter particles.

Description:

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to the field of photodetector array
devices. More particularly, methods are provided for placing arrays of
spectroscopic filter material on photodetector arrays such as image
sensors and focal plane arrays.

[0004] 2. Background of the Invention

[0005] Compact, low-cost digital imaging systems that combine the benefits
of high spatial and spectral resolution are in demand for the next
generation of analytical and surveillance instruments. Advances in
commercial image sensors ("camera chips") and infrared focal plane arrays
have led to picture element ("pixel") densities with very high spatial
resolution. Despite pixel densities sufficient to resolve ultrafine
features with large fields of view, commercially available color CMOS and
CCD cameras are still limited in the degree of spectral (chromatic)
resolution. Likewise, spectroscopic imaging outside the visible spectrum,
either in the ultraviolet or the infrared is rarely accomplished at the
photodetector level. Instead, spectral resolution of color imaging
systems is generally restricted to the Bayer red-green-blue (RGB) color
filter array (CFA) mosaic pattern found on virtually all color image
cameras. These color cameras are designed to meet minimal color
reproduction requirements for digital photography, but are in no way
optimum, for example, in bioanalytical instrumentation used to perform
medical or scientific analyses. In typical instrumentation, more precise
definition of spectral bands is achieved with a combination of a
gray-level monochrome image sensor and one or more dispersive or
absorptive filter elements that are bulky and expensive, particularly
when motorized switching between filter sets is employed. Likewise,
electronically-tunable filters (e.g. LCD, acousto-optic, Fabry-Perot,
etc.) reduce image acquisition speed and do not yield high spectral
fidelity or efficient light throughput. Elimination of external
dispersive elements and slow tunable filters requires directly
integrating higher spectral definition into the mosaic pattern on the
surface of the photodetector array, which may be silicon CMOS/CCD in the
ultraviolet and visible spectral range, InGaAs in the near infrared
radiation (NIR) range and short wave infrared radiation (SWIR) range,
InSb in the mid wave infrared radiation (MWIR) range and HgCdTe in the
long-wave, or far infrared radiation (LWIR) range. The photodetector
array may not be an array of photodiode pixels and may consist of arrays
of bolometer or pyroelectric detectors, for example. In addition, the
photodetector array may be a structured ensemble or layered arrangement
of discrete detectors or photodetector arrays, perhaps sensitive to
wavelengths in a variety of spectral bands.

[0006] What is needed is a process for expanding the number of detected
spectral intervals, and increasing spectral resolution, spectral range,
and sensitivity dynamic range of photodetector arrays through batch
assembly of filter arrays directly on the surface of the photodetector
array, or onto a substrate or stamp that can be either applied to or used
to transfer the filter array to the photodetector array surface.

BRIEF SUMMARY OF THE INVENTION

[0007] A method of manufacture using biomolecular binding forces to
assemble micro- and nanoscale structures into an array of functional
spectroscopic filters is provided. Precisely positioned functional filter
elements at specific locations in an array may be formed by binding of
complementary biomolecules that carry filter particles to anchored
biomolecules on addressable regions of a photodetector array surface.
Biomolecular binding directs the filter particles to specific array
locations during a batch binding step. Multilayers of registered micro-
or nanoscale particles may also be fabricated.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The invention may be better understood by reference to one or more
of these drawings in combination with the detailed description of
specific embodiments presented herein.

[0009] FIG. 1 illustrates the process for making filter particle arrays
using a biomolecular assembly process.

[0010] FIGS. 2A, 2B, 2C, 2D and 2E are isometric views showing an example
of a filter particle array at various stages of assembly.

[0012] FIGS. 4A, 4B, 4C and 4D are cross-section views of a filter
particle array made by the addition of different particles, represented
by different shadings and sizes, during multiple attachment steps.

[0013]FIG. 5 is a schematic showing the process for using, a stamp
substrate to assemble a filter particle array and transfer the array to
addressable regions of a photodetector array.

[0014] FIG. 6 is a cross-section view illustrating light filtering
performed by a filter particle array having four different types of
filter particles affixed at four addressable regions of the photodetector
array. The filter particle array is detached from the substrate in the
drawing to increase clarity.

[0015] FIG. 7 is a photograph showing a specific example of nucleic
acid-mediated assembly of polymer microsphere particles to specific
regions of an addressable array.

DETAILED DESCRIPTION OF THE INVENTION

[0016] A method for using the principles of microarrays in a different
technology to construct functional, mechanical devices is disclosed
herein. In a preferred embodiment of the invention, nucleic acid, or DNA
microarrays are used to fabricate filter particle arrays through
biomolecule-guided assembly of the filter particles to specific regions
of the microarray. Biomolecule-guided assembly of filter particles is
performed by first synthesizing or otherwise fabricating a microarray.

[0017] Microarrays, or "arrays," are well known and widely used in
molecular biology. Arrays used in embodiments of the invention can be,
for example, arrays of proteins, peptides, antibodies, antigens,
aptamers, nucleic acids, ligands, receptors, chemical compounds, or
arrays of other biomolecules. Numerous examples of how to make these
types of arrays and useful substrate surfaces can be found in Platt et
al., 2009; Chabra et al., 2007; McCauley et al., 2003; Ivanov et al.,
2004; Stadler et al., 2007; Oleinikov et al., 2003; U.S. Pat. No.
7,297,497; U.S. Publication Nos. 2004/0072274, 2007/0015213,
2004/0038307, 2005/0095649, 2008/0293591, 2009/0018027, as well as WO
2003/095469A1. Microarrays entail binding between anchored probe
biomolecules that are coupled to a surface and target, or complement
biomolecules. A type of microarray is a DNA or an RNA microarray. DNA
microarrays consist of an arrayed series of thousands of microscopic
areas of DNA oligonucleotides, each containing a specific DNA
sequence--called an anchored probe. Hybridization between anchored probe
biomolecule sequences and complementary target sequences in solution is
detected by various ways to indicate the relative abundance of nucleic
acid target sequences in the sample. Methods and apparatuses for
preparing DNA microarrays are well known in the art. DNA microarrays are
commercially available from numerous providers.

[0018] Referring to FIG. 1, methods for using the binding properties of
biomolecular arrays to manufacture a spectroscopic filter array device is
illustrated. In this process, a substrate is supplied in step 101. The
substrate may be a photodetector array such as a commercial image sensor
or focal plane array, for example. Alternatively, the substrate may be a
glass or other transparent plate that is non-interacting with the full
range of spectral bandpass of the filter array. In another embodiment,
the substrate may be an intermedate transfer stamp used to assemble the
array and transfer the assembled array to a second substrate such as a
photodetector array. In step 102, an array of biomolecules is formed on
the substrate from step 101. Multiple methods are known in the art for
populating biomolecules onto surfaces into arrays including methods that
involve spotting oligonucleotide or peptide sequences, or alternatively
synthesizing oligonucleotides or peptides in situ via single nucleotide
or amino acid coupling.

[0019] By way of example, the method of Photo-Generated Reagent (PGR)
provided in U.S. Pat. Nos. 6,426,184; 7,491,680; 7,544,638; and
7,838,466; and U.S. Patent App. Pub. No. 2007/02246216 may be used. A
microfluidic device cover is placed over the supplied substrate. The
device includes many reaction chambers, which are sized and arranged so
as to register with the image sensor array to which the filter is to be
applied. Photo-generated reagent is formed by illumination with light in
specific fluid compartments throughout the array. Light provides a means
to activate a chemical process that results in acid generation, which
enables synthesis of part of a DNA molecule when a nucleotide solution
flows across the array in a subsequent step. Areas where no light
exposure occurs do not react in that step. The process is repeated until
each array area is populated with sequences of biomolecules, referred to
as anchor probes. Because the position of the light illumination is
chosen during manufacture of the array, the sequence of each anchor probe
in the collective set in the array is known and recorded as a library of
the anchor probes.

[0020] Because the sequences of the set of anchor probes are known for
each position in the array, complementary binding sequences to those
probes are used to direct the attachment of filter particles to specific
locations in the array from the dispersion of filter particles supplied
in step 103. In embodiments of the invention, a filter particle may
comprise a "bead" or "polymer sphere" or "microsphere" that is capable of
being "dyed" or "colored" or enriched with other smaller particles or
pigments that can alter the spectroscopic properties of the particle
core. Core modification may include covalent coupling of molecular dye
molecules, nanoparticles, ionic complexes and other
electromagnetically-active moieties in such a fashion that the particle
acts as a carrier of the spectroscopic-selective pigment.

[0021] In other non-limiting examples, the particle may consist of a block
co-polymer bearing a pendant dye molecule that is incorporated during
synthesis of the particle, or physical partition of the dye, or pigment
by hydrophobic swelling and core diffusion. Core-dyed microspheres are
available from a number of vendors, with custom swelling and dying
processes readily available (e.g. Bangs Laboratories; Fishers, Ind., USA,
www.bangslabs.com). Suitable compositions of polymer beads are numerous
and will vary depending on the application and whether or not an
additional particle is attached to the bead. U.S. Pat. Nos. 6,268,222;
6,327,410; and 7,335,153, U.S. Publication Nos. 2002/0146745 and
2006/0068504, and PCT Publication No. WO/2002/103371 describes numerous
non-limiting examples of bead and particle compositions suitable for
embodiments of the invention.

[0022] In other embodiments, the pigment may be colored, ultraviolet- or
visible-absorbing, or fluorescent nanoparticles may be covalently coupled
or physically partitioned into the core of the polymer microsphere. In
still other aspects of the invention, chemical group vibrational
absorption may impart differential spectroscopic filter properties in the
MWIR. Spectral selection in the LWIR range may be thermally or
bolometrically detected by concentrating varying amounts of molecules
with specific vibrational wavelengths within the particles. Further
still, spectroscopic altering particles such as lanthanide-doped yttrium
oxide upconverting phosphors that absorb infrared radiation and re-emit
to shorter wavelengths may be present in the particles.

[0023] Particles, beads, spheres, or microspheres need not be spherical.
Particles may be of any geometrical shape or may be irregularly shaped.
Particles may also be solid, hollow, or porous and may be composed of
more than one material or substance or numerous layers of substances.
Particle sizes may range from nanoscale, on the order of nanometers
(e.g., less than or equal to about 100 nm), to millimeter scale (e.g.,
less than or equal to about 1 mm). In embodiments of the invention,
particles of mixed sizes may be used for making a filter particle array.
By way of example, U.S. Pat. Nos. 6,327,410 and 7,335,153, and U.S.
Publication Nos. 2002/0146745 and 2006/0068504 describe numerous bead and
particle compositions and sizes suitable for embodiments of the
invention.

[0024] In all embodiments, the microsphere is modified, derivatized, or
functionalized with the dye or pigment or spectrally-selective molecule
so as to be capable of interacting with select spectroscopic regions of
electromagnetic radiation relative to the whole spectrum. The range is
not limited to any particular region of electromagnetic radiation,
provided a suitable spectroscopic interaction is imparted by the
assembled filter particle array.

[0025] Assembly of filter particle arrays shown in FIG. 1 step 104 begins
with attaching complementary sequences to particles, thereby forming a
"filter particle complex." As used herein, the term "filter particle
complex" refers to filter particles having a moiety attached thereto that
mediates binding to a complementary moiety on a surface. In the present
embodiment, a binding moiety comprises a nucleic acid that is
complementary to a nucleic acid of a nucleic acid array on the substrate
supplied in step 101. In other non-limiting examples, a binding moiety
may comprise biotin, streptavidin, or another chemical entity capable of
interacting with a complementary entity of an array on a surface.

[0026] In certain embodiments of the invention, a filter particle complex
comprises a filter particle attached directly to a binding moiety.
Non-limiting examples of direct binding include nucleic acid fragments,
polynucleotides, oligonucleotides, proteins, peptides, ligands,
receptors, antigens, antibodies, and individual members of biological
binding pairs. In other embodiments, a filter particle complex comprises
a linking structure that connects the particle to the binding moiety. For
example, a filter particle may be attached directly to a nucleic acid or
through a linking moiety such as a terminal amine or carboxylate group,
or through multiple linking moieties, such as, for example, biotin and
streptavidin. Methods for the attachment of various binding moieties to
particles are known in the art (see e.g., U.S. Publication Nos.
2002/0028455 and 2002/0146745 and U.S. Pat. No. 6,327,410).

[0027] Once individual complementary sequences specific to anchor probes
in the array are coupled to the surface of individual filter particles, a
subset of particles for each type of filter particle is combined into a
master mixture or dispersion of multiple types of filter particles (FIG.
1. step 105). This dispersion contains all of the filter particle
elements that are desired for manufacture of a particular pattern of a
filter particle array. In step 105, exposure of the dispersion of
particles to the anchor probe microarray on the substrate will lead to
assembly of each filter particle element into the pre-designed pattern,
or mosaic pattern. This occurs during a single batch step, regardless of
the dimensions of the array. The assembly process may be repeated as
needed with yet a further set of filter particles that is complementary
to the first set of particles to increase the thickness of the filter
particle array.

[0028] As a final measure illustrated in step 106, post processing steps
such as washing to remove non-assembled particles, annealing and addition
of special function layers such as spin-on of a final index matching
fluid or optical cement, for example, will provide the final structure of
the filter particle array. If the chosen substrate is an image sensor or
glass slide that is inverted and applied to the surface of the image
sensor, the filter particle array pattern can impart any combination of
enhanced spectral selectivity, expanded spectral range, and expanded
sensitivity dynamic range to the device compared to existing methods for
fabricating filter arrays known in the art.

[0029] FIG. 2A shows substrate 201, upon which a nucleic acid array can be
synthesized. The substrate may comprise a photodetector array where the
nucleic acid array is synthesized directly onto the surface of individual
photodetector elements, for example. In another embodiment, the substrate
may comprise a material with special function such as a glass slide for
optical transparency. The filter array on a special function substrate
may be joined with the photodetector array by positioning the filter
array in contact with, and registered to, the photodetector array. In
another embodiment, the substrate may comprise a stamp that can be used
to transfer the pattern in a subsequent step. Substrate 201 may include
any number of layers that may be used to enhance or protect the response
of the photodetector relative to the filter.

[0030] In the embodiment where the filter array is deposited directly on
the photodetector array, it may be present on the entire array surface or
on selected regions of the photodetector array. In most embodiments, the
filter array is registered one-to-one with each pixel in the
photodetector array. However, one-to-one registration, defined as the
condition when the spatial area covered by filter particles of a single
type corresponds exactly with the area of a single photodetector pixel,
is not required. Alternate embodiments include a single filter particle
array region that is registered to multiple photodetector pixels and need
not have square dimensions.

[0031] FIG. 2B shows distinct, arrayed nucleic acid sequences 203A-D, the
"microarray", attached to substrate 201 that defines addressable regions
204A-D of a "unit cell" 205 of the filter particle array. Filter particle
complexes, shown in FIG. 2C, have filter particles 206A-D with each
particle type having nucleic acids 207A-D that are complementary to
nucleic acids 203A-D in one section of unit cell 205. FIG. 2D shows the
assembled unit cell 205 following hybridization of complementary nucleic
acids 207A-D on filter particles 206A-D to the anchored nucleic acids
203A-D in the microarray. For clarity, the nucleic acids on particles
that do not participate in hybridization to the microarray are not
depicted in the diagram. Such nucleic acids are available for binding
additional particles in subsequent steps of filter particle array
assembly.

[0032] During assembly, it is preferred to employ varying conditions of
hybridization to achieve varying degrees of selectivity of nucleic acid
207 toward anchored nucleic acid 203. In a non-limiting example,
hybridization of a related nucleic acid that does not hybridize to a
complementary or partially complementary nucleic acid under stringent
conditions may be achieved by hybridization at low temperature and/or
high ionic strength. Such conditions are termed "low stringency" or "low
stringency conditions," and non-limiting examples of low stringency
include hybridization performed at about 0.15 M to about 0.9 M NaCl at a
temperature range of about 20° C. to about 50° C. Because
hybridization sequences 203 are predefined and not constrained to any
particular sequence such as required for DNA detection methods, selection
can be made to minimize sequence hybridization interference. It is within
the skill of one in the art to select appropriate non-interfering
sequences and further modify the low or high stringency conditions to
suit a particular application.

[0033] FIG. 2E shows how unit cell 205 can be repeated to form a larger
filter particle array 208. The diagram illustrates filter particle array
208 comprising a series of filter particle subunit regions (i.e., "unit
cells") 205A-N. The illustration depicts the stage following removal of
the nucleic acids and after other potential conditioning steps such as
heating, reflowing, chemical fusion or addition of a continuity layer,
such as an index matching layer. For clarity, the collection of filter
particles 206 for any given addressable region is represented
schematically as flattened cubes or squares.

[0034] FIG. 3A illustrates the embodiment where filter particle array unit
cell 205, consisting of filter particles 206A-D, is deposited on
substrate 201 that comprises a photodetector array 301. Photodetector
array 301 may consist of addressable detector elements 302 such as pixels
of an image sensor or focal plane array. Alternatively, photodetector
array 301 may be composed of an array of bolometers or pyroelectric
detectors. An intermediate layer 303 such as a protective oxide coating
or a registered array of refractive structures (lenslets) on
photodetector array 301 may be included. Intermediate layer 303 may also
consist of, for example, a custom linkage layer for attachment and
positioning of nucleic acids above the surface of the photodetector
array. As a final measure, a protecting outermost layer 304 may be used
to complete the filter particle array assembly 305. Outermost layer 304
may protect the filter particle array from physical damage, or condition
the filter particle array for a specific application such as matching the
index of refraction to an external medium to decrease light reflection or
scattering from individual particles. FIG. 3B illustrates an embodiment
where filter particle array unit cell 205 is deposited first on substrate
201, shown at the top of the stack. As an example, substrate 201 can be a
material such as a transparent glass or quartz plate for image sensor
applications. Numerous possibilities exist for the composition of
substrate 201. In the embodiment depicted in FIG. 3B, filter particle
array unit cell 205 would be arranged such that 205 would first be
deposited on substrate 201, inverted, registered to, and placed in
contact with photodetector array 301. The face of substrate 201 not
having the filter particle array attached thereto would serve as the
outermost layer of the assembled filter particle array device 305.

[0035] In some embodiments, attachment of filter particles 206 to
photodetector array 301 bearing microarray 203A-D is performed more than
once to form multilayers. This may involve repeatedly performing the
hybridization step with the same type of particles so as to increase the
number density of a specific type of particle 206 in filter particle
array 208. In other embodiments, the hybridizing step is repeatedly
performed with one or more different types of particles. All hybridizing
steps may be repeated one or more times until the desired density of
filter particles 206 is achieved. FIG. 4A shows a cross section view of
photodetector array 301 having four addressable regions 204A-D consisting
of four addressable detector elements 302A-D, each detector element
having a distinct nucleic acid sequence represented by 203A-D that is
attached to the surface of photodetector array 301 of FIG. 3. FIG. 4B
shows the attachment of four different particle types 206A-D to each of
the four addressable regions 204A-D. Nucleic acids 207A-D attached to
filter particles 206A-D may mediate attachment of additional particles
401A-D bearing nucleic acids 402A-D that are complementary to nucleic
acids 207A-D attached to particles 206A-D (FIG. 4C). FIG. 4D shows the
further attachment of additional particles 403A-D in another
hybridization step mediated by nucleic acids 404A-D complementary to
nucleic acids 402A-D (FIG. 4C).

[0036] In another embodiment, illustrated in FIG. 5, filter particle array
208 may be formed on a substrate which consists of transfer stamp 501.
Transfer stamp 501 may be used to first assemble filter particle array
208, then transfer assembled filter particle array 208 to another
substrate such as photodetector array 301. The process begins with the
assembly of microarray 203A-D on transfer stamp 501. Transfer stamp 501
may have a planar surface, or may contain relief structure for assisting
in release. Transfer stamp 501 is immersed in fluid vessel 502, which
contains the dispersion of filter particles 206A-D bearing complementary
nucleic acids 207A-D. Immersion of transfer stamp 501 results in assembly
of filter particle array 208 on transfer stamp 501 via step 503. Transfer
stamp 501 bearing filter particle array 208 can then be brought in
contact with a second substrate such as photodetector array 301
illustrated in step 504. Photodetector array 301 may contain an adhesion,
or linking layer 505 that promotes release and transfer of the assembled
filter particle array to photodetector array 301 from transfer stamp 501.
In a preferred embodiment, linking layer 505 is a thin adhesive that
serves to seat assembled filter particle array 208 during contact.

[0037] Other methods for transferring a filter particle array may include
encapsulation of the assembled array in a protective coating such as a
hydrogel, or an oligosaccharide or polysaccharide coating, followed by
stamping onto photodetector array 301 and subsequent removal of the
hydrogel or coating, if desired. As a non-limiting example,
ultra-low-melting temperature agarose is a thermo-reversible, physically
cross-linked hydrogel that can be used for encapsulating and transferring
an array. Following transfer to photodetector array 301, the agarose can
be re-melted at 50-55° C. so as to release the filter particle
array while retaining the integrity of filter particle array 208 and the
activity of the filter particles.

[0038] In yet another example, a saccharide solution such as 1% trehalose
may be dried or lyophilized onto the filter particle array 208 to
maintain its integrity during transfer to another substrate. Rehydration
following transfer can be used to remove the saccharide solution. In some
aspects, it will be useful to rehydrate the saccharide in a solution that
maintains hybridization between complementary nucleic acids.

[0039] In most transfer methods, it will be desirable to perform a
denaturation step to facilitate release of hybridization. Hybridization
release serves to separate the assembled particles by releasing the
chemical energy in the hybridization bonding. Secondly, denaturation
serves to keep the microarray intact for re-use and re-assembly of
additional layers or depositing onto additional substrates. Upon melting
or chemical denaturing of the hybridized DNA complex, assembled filter
particle array 208 preferentially remains on photodetector array 301.
Chemical denaturation may involve specific denaturing agents such as high
salt, or low salt environments or other specific intercalants. Methods
for controlled denaturation of hybridized nucleic acids are numerous and
well known in the art.

[0040] Following denaturation of nucleic acids 207, and/or linking layer
505, the filter particle array will adhere in sine to the surface on
which it was transferred. In the preferred embodiment, separation of
stamp 501 from photodetector array 301 leaves an intact microarray 203 on
the surface of transfer stamp 501. Stamp 501 can then be used in a
repetitive manner to assemble additional filter particle arrays 208 as
illustrated by step 506 in FIG. 5. This process could include the
addition of multiple layers of the assembled filter particle array onto
the same substrate. Deposition of repeated multiple layers onto
photodetector array 301 is illustrated schematically in the cyclic
process step 507. The schematic representing step 507 illustrates
photodetector array 301 with three transferred layers of assembled filter
particle array 208 forming filter particle array assembly 508.

[0041] Following transfer of a single, or multiple assembled filter
particle array(s) 208 to photodetector array 301, the device may then
receive final processing treatments including any special function layers
such as protection or index-matching layers, step 510. At any point in
the process removal of nucleic acids 203 or linking layer 505 may occur,
if necessary. A number of chemical agents for degrading nucleic acids as
well as high temperature exposure can lead to nucleic acid removal. The
adhesive layer may be left intact in the final device setting or be
removed by chemical degradation, treatment with irradiation such as UV
irradiation, or burning or ashing in the case where the
spectrally-selective pigment is tolerant to high temperatures and remains
intact after processing.

[0042] Physical features present on the surface may maintain the integrity
of the assembled filter particle array. The nature of the material
interaction may provide sufficient structural integrity for the filter
particle array to be separated from the substrate and function as a
stand-alone film, either independent or assisted by a common layer that
provides backing support. As non-limiting examples, this may include
deposition of a common layer such as an index-matching film that
partially, or entirely covers the filter particle array. An
"index-matching material" or "refractive index matching film," is a
substance that has an index of refraction that closely approximates that
of an optical element and is used to reduce Fresnel reflection at the
surface of the element. index-matching material is usually a liquid,
adhesive, or gel. For example, an index-matching layer may be used in
methods of the invention to decrease reflectance of light incident on the
particles of a light filter array. Index-matching material may be
deposited on light filters of the invention by, for example, spin-coating
techniques known in the art. Index-matching materials are commercially
available (e.g., Newport Corp.; Irvine, Calif., USA and Cargille Labs;
Cedar Grove, N.J., USA).

[0043] In all embodiments, it is desirable to maintain the functionality
of the filter particles and the functionality and integrity of the filter
particle array. As used herein "integrity" means whole, undivided, or
undiminished. Alternatively, the array substrate or sections thereof may
be surrounded by raised regions of the surface such that filter particles
are physically constrained. Exemplary methods for the derivatization of
substrates and particles for purposes of attachment of particles to
surfaces are described in U.S. Pat. Nos. 6,327,410 and 7,335,153 and U.S.
Publication Nos. 2004/0248144 and 2002/0146745. Filter particle arrays
may be transferred to or from any type of surface. In this aspect, it is
desirable that the act of transferring maintains the array integrity. In
some aspects, transferring an array to a different surface may enhance
the usefulness or operability of the array, and may increase the
manufacturability, since the microarray template used to assembly the
filter particle array may be repeatedly used to assemble and transfer
filter particle arrays to multiple devices.

[0044] Filter particle arrays that filter different wavelengths of
electromagnetic radiation and methods for making and using spectroscopic
filter arrays are illustrated in FIG. 6. A spectroscopic filter array
functions to remove one or more wavelengths of electromagnetic radiation
from a broad spectrum of radiation 601 passing through the filter. One
example of a spectroscopic filter array is a color filter array (CFA). A
CFA filters visible light by wavelength range such that certain
wavelengths of light pass through specific regions of the CFA while other
wavelengths are prevented from passing through those regions of the CFA.
In some aspects, one or more wavelengths of light or a range of
wavelengths may pass through certain regions of a filter array while
other wavelengths of light or other ranges of wavelengths pass through
other regions of the array. Therefore, a CFA may have one or more regions
that removes or reduces specific wavelengths or colors of light from the
spectrum and/or that provides a means for certain wavelengths or colors
of light to traverse an array region. In another embodiment, a filter
array may be constructed that filters different wavelengths of far
infrared radiation, for example, a pattern on top of a HgCdTe detector
array. The assembly method of the invention could be broadly applied to
any portion of the electromagnetic spectrum provided particles are
selected for interaction with the target radiation range.

[0045] FIG. 6 shows representations of a photodetector array 301 having
four addressable detector elements 302A-D representing four addressable
regions 204A-D. Spectroscopic filtering by unit cell 205 of filter
particle array 208 that is composed of four unique filter particle
elements 206A-D is illustrated in cross section. Filter particles 206A-D
is shown attached to photodetector array 301. Broadband electromagnetic
radiation 601 impinges on filter particle array unit cell 205. This
assembly is represented in FIG. 3A, however the substrate with assembled
filter particle array 208 is shown detached from photodetector array 301
for clarity. In practice, these two components would be in close contact.
Particles 206A-D filter unwanted wavelengths of the broad spectrum 601,
consistent with the pre-selected filter spectroscopic element in
particles 206A-D, while providing a means for the passage of respective
wavelengths 602A-D of broad spectrum 601. For example, particle 206A may
pass only short wave radiation 602A (e.g. 300 nm light). This radiation
would be the only component reaching the corresponding detector element
302A in addressable region 204A of photodetector array 301. Another
assembled set of particles 206D, for example, would pass only longer
radiation 602D (e.g., 1.5 μm), to detector element 302D in addressable
region 204D and so on for other addressable filter particle array regions
204 in filter particle array unit cell 205. In practice, the level and
range of filter selectivity is defined by the arrangement of unit cell
205, which may be repeated to form the mosaic pattern of filter particle
array 208. The ability to create large and complex arrays with multiple
constituents in the fashion presented by this invention is not known in
the art.

[0046] FIG. 7 shows photographs of specific examples of polymeric
microsphere particles that are localized at various regions in filter
particle array 208. In this example, filter particle array 208 was
assembled using a custom DNA microarray synthesized by Roche Nimblegen
(www.nimblegen.com). Initially, microarray 701 was synthesized with
anchored probe sequences 203A-D defined for specific regions 204A-D in
the microarray. This method is one of many methods known in the art for
microarray synthesis. Filter particle array 208 was formed on microarray
701 when filter particles 206 bound to specific regions 204A-N. In
example 701, a 2×2 array is illustrated with two of the filter
particle array regions, 204A and 204D having bound particles with
different concentrations of core dying. A terminal edge of the array is
also illustrated at the top of 701 where, in this specific example, full
particle binding area 702 was encoded. Inset 703 shows unit cell 205 of
filter particle array 208, composed of filter particle addressable
regions 204A-D. The schematic diagram in inset 704 further illustrates
unit cell 205, composed of addressable regions 204A-D. In the schematic,
complementary sequences 207A-D, which were attached to polymer
microsphere particles 206A-D, hybridized to anchored sequences 203A-D
present in each array region 204A-D. Particle set 206A and 206D were
localized in the example and regions 204B and 204C did not hybridize. For
clarity, only the front row of particles 206 are depicted with
complementary sequences 207. In practice, particles may be localized in
any or all of the areas by combining individual particle sets 206A-N
(N=any number of possible combinations) into a disperion of particles
with requisite encoding sequences 207A-N and exposing the particles to
microarray 701 in a batch process.

[0047] In the example shown in FIG. 7, localized particles 206 appear as
shaded areas, e.g., 204A, of the addressable regions of filter particle
array 208. This is contrasted with the lighter region 204C where no
localization occurs during exposure. Photograph 705 shows a different
array consisting of a 3×3 unit cell 205 that is repeated to form
filter particle array 208. In this example, particles 206A-I bound to
addressable regions 204A-I consisting of polymer microspheres that were
core-dyed with fluorescence dyes and nanoparticles. Photograph 705 shows
brightly shaded regions where the core dying was extensive. Other regions
where particles with less concentration of fluorophore were localized can
also be seen in the photograph. Addressable regions 204, where no
complementary particles are bound, appear dark in the photograph. In this
example, the edge of microarray 701 is depicted with a portion of
non-array area 702 in view.

[0048] A filter particle array may be a Bayer CFA (U.S. Pat. No.
3,971,065). A Bayer CFA of the invention comprises an alternating pattern
composed of one red, two green, and one blue filter, each covering a
single image sensor. This type of pattern is referred to as a 2×2
pixel pattern, because the pattern has 4 pixels in a 2×2
arrangement. In other embodiments, filter particle arrays are made to
have 3×3 pixel patterns, 4×4 pixel patterns, 5×5 pixel
patterns and/or up to N×N pixel patterns, where N is limited by the
number of addressable spots present on the nucleic acid array used for
making the filter particle array. In still other aspects of the
invention, filter particle arrays comprise one or more different pixel
patterns. Expanding the size of the pixel pattern from a typical
2×2 pattern to a 3×3, 4×4, 5×5, or higher pixel
pattern enables expansion of a spectroscopic mosaic set beyond the
standard RGB and CMYK patterns currently used in filtering systems for
cameras and other optics. The expanded mosaic pattern may include filter
particles such as upconverting phosphors that absorb light in the near-IR
and transmit in the visible, or may include nanoparticles of PbSe which
may absorb certain spectroscopic regions of NIR and SWIR. Furthermore,
array dimensions may not be square or symmetric, for example a repeated
2×3, 2×4, 2×5, 2×7, 2×10, 2×17,
2×51, 2×200, 2×1000, 3×4, 3×9, 3×300,
10×100 may be created. Furthermore, array dimensions need not be
rectangular. Polygonal e.g., hexagonal or octagonal unit cells, or other
irregularly shaped or elongated unit cell can be used to create filter
particle arrays using the method of the invention. In all embodiments,
higher spectral definition, higher color fidelity, and higher resolution
of a spectroscopically richer set of closely matched wavelengths of light
is provided. High spectral definition is important in applications such
as laser threat detection or biological sample staining, for example.

[0049] A non-limiting example of a means for detecting filtered light is a
color-imaging detector or color camera. Color-imaging detector as used
herein refers to any component, portion thereof, or system of components
that can detect colored light. Non-limiting examples of color-imaging
detectors can be found, for example in U.S. Publication No. 2006/0252070.
In aspects of the invention, a color-imaging detector may be positioned
for detecting filtered light, for example, beneath a color filter array
or on a side of the color filter array. In another aspect of the
invention, the substrate of a filter particle array comprises a color
imaging detector. The methods described in the invention are not limited
to filtering of color or visible light. Filter particle arrays composed
of requisite selective infrared absorbing regions can be fabricated on
focal plane arrays. Infrared focal plane arrays are manufactured for
different regions of the infrared ranging from NIR to LWIR. Infrared
focal plane arrays are commercially available (e.g., Goodrich; Princeton,
N.J., USA and FLIR Systems Inc.; Boston, Mass., USA).

[0050] It is understood that modifications to the invention may be made as
might occur to one skilled in the field of the invention within the scope
of the appended claims. All embodiments contemplated hereunder which
achieve the objects of the invention have not been shown in complete
detail. Other embodiments may be developed without departing from the
spirit of the invention or from the scope of the appended claims.
Although the present invention has been described with respect to
specific details, it is not intended that such details should be regarded
as limitations on the scope of the invention, except to the extent that
they are included in the accompanying claims.